Biological materials such as cells, proteins and vaccines are frequently preserved by lyophilizing aliquots of a liquid composition containing the biological material. The lyophilization process involves freezing a liquid sample which is then subjected to a vacuum so that the ice in the frozen sample directly changes to water vapor or sublimes. After the removal of ice, the sample temperature is gradually increased (while still under vacuum) and water is desorbed from the remaining non-ice phase of the sample.
Lyophilized cakes of a biological material are prepared by aliquoting into a glass container a desired amount of the biological material, which is typically present in a buffered solution with appropriate stabilizers (i.e., a “formulation”) and then subjecting the glass container containing the biological material to steps of cooling, freezing, annealing, primary drying and secondary drying. The glass container containing the dried biological material is typically stored for long periods of time at room temperature or under refrigerated conditions. The dried formulation containing the biological material is typically reconstituted by adding a liquid, usually water, to the glass container. Glass containers used for lyophilizing biological materials intended for use as therapeutics and vaccines typically have included glass vials and dual chamber injection devices, in which one chamber contains the lyophilized cake and the other chamber contains the reconstituting liquid.
Methods of lyophilizing biological materials in the form of spherically shaped pellets, (referred to as lyospheres or i.e., beads), have also been described. See, e.g., International Patent Application Publication Nos. WO 2009/092703, WO 2010/125087, and WO 2013/066769. In these methods, individual samples of the biological material are frozen and dried prior to placing a desired number of the dried samples into a storage container such as a glass vial. Historically, these methods relied on either (a) dispensing an aliquot of a liquid composition containing the desired amount of a biological material into a container of a cryogen such as liquid nitrogen, which results in direct contact of the biological material with the cryogen and/or (b) dispensing an aliquot of a liquid composition containing the biological material into a cavity present on a chilled solid plate, where the cavity contains the aliquot until it is frozen. Another approach, which is referred to as the die and punch method and uses a closed mold and compressive force to obtain a frozen pellet, suffers from a complex assembly design, leakage of fluid formation from the cavity and sticking of pellet to either the die or the punch.
Microwave vacuum-drying is a rapid method that can yield products, such as foods, plants and biological materials, with improved stability compared to air-dried and freeze-dried products. Because the drying is done under reduced pressure, the boiling point of water and the oxygen content of the atmosphere are lower, so food or medicinal components sensitive to oxidation and thermal degradation can be retained to a higher degree than by air-drying. See, e.g., U.S. Pat. Nos. 4,389,794; 4,664,924; 4,809,596; 4,882,851; 6,128,321; 6,956,865; and International Patent Application Publication Nos. WO 02/103407; WO 2009/033285; WO 2009/049409; and WO 2013/010257.